Interaction of protein synthesis initiation factor 2 from Xenopus laevis oocytes with GDP and GTP analogs

AbstractThe structural specificity of the purified protein synthesis initiation factor 2 (eIF-2) from X. laevis ovary towards analogs of GTP and GDP was studied. The relative affinity of the structural analogs was measured by their capacity to inhibit the formation of the [3H]GDP·eIF-2 binary complex. The results obtained demonstrate that modifications in the ribose moiety are well tolerated by eIF-2 which binds dGTP, 2′,3′-dialdehyde GTP (oGTP) and 2′,3′-dialdehyde GDP (oGDP) and even the dinucleotide cytidylyl(5′-3′)guanosine 5′-triphosphate (pppGpC). Substitution in the polyphosphate chain by phosphorothioate groups in the β and γ positions (GDPβS or GTPγS) does not abolish the affinity for the nucleotides and the presence of an imido group between the β and γ phosphates in guanyl-5′-yl imidodiphosphate (GppNHp) still permits a weaker but significant binding. Guanine 5′-O-(2-fluorodiphosphate) (GDPβF) has an affinity considerably lower than GDPβS. Methylation of position 7 of the guanine (7-m GDP), however, completely eliminates the interaction of GDP with eIF-2. The analogs tested can be listed in the following order of descending affinities: GDP > GDPβS > oGDP⩾ GTPγS > GDPβF > pppGpC > GTP > GppNHp > oGTP ⪢ 7-m GDP. Assays of the capacity of GTP analogs to form a ternary complex of the type met-tRNAi·GTP·eIF-2 or of GDP analogs to inhibit the formation of this complex reflect, in general, the same order of relative affinities except for pppGpC, which is weaker in its capacity to form a ternary complex than GppNHp or oGTP, although it has a higher affinity than these compounds in the formation of a binary complex

BRCA1 and BRCA2 founder mutations account for 78% of germline carriers among hereditary breast cancer families in Chile.

Identifying founder mutations in BRCA1 and BRCA2 in specific populations constitute a valuable opportunity for genetic screening. Several studies from different populations have reported recurrent and/or founder mutations representing a relevant proportion of BRCA mutation carriers. In Latin America, only few founder mutations have been described. We screened 453 Chilean patients with hereditary breast cancer for mutations in BRCA1 and BRCA2. For recurrent mutations, we genotyped 11 microsatellite markers in BRCA1 and BRCA2 in order to determine a founder effect through haplotype analysis. We found a total of 25 mutations (6 novel) in 71 index patients among which, nine are present exclusively in Chilean patients. Our analysis revealed the presence of nine founder mutations, 4 in BRCA1 and 5 in BRCA2, shared by 2 to 10 unrelated families and spread in different regions of Chile. Our panel contains the highest amount of founder mutations until today and represents the highest percentage (78%) of BRCA1 and BRCA2 mutation carriers. We suggest that the dramatic reduction of Amerindian population due to smallpox and wars with Spanish conquerors, a scarce population increase during 300 years, and the geographic position of Chile constituted a favorable scenario to establish founder genetic markers in our population

Haplotype analysis of the internationally distributed BRCA1 c.3331_3334delCAAG founder mutation reveals a common ancestral origin in Iberia

Background: TheBRCA1c.3331_3334delCAAG founder mutation has been reported in hereditary breast and ovarian cancer families from multiple Hispanic groups. We aimed to evaluateBRCA1c.3331_3334delCAAG haplotype diversity in cases of European, African, and Latin American ancestry. Methods: BC mutation carrier cases from Colombia (n = 32), Spain (n = 13), Portugal (n = 2), Chile (n = 10), Africa (n = 1), and Brazil (n = 2) were genotyped with the genome-wide single nucleotide polymorphism (SNP) arrays to evaluate haplotype diversity aroundBRCA1c.3331_3334delCAAG. Additional Portuguese (n = 13) and Brazilian (n = 18) BC mutation carriers were genotyped for 15 informative SNPs surroundingBRCA1. Data were phased using SHAPEIT2, and identical by descent regions were determined using BEAGLE and GERMLINE. DMLE+ was used to date the mutation in Colombia and Iberia. Results: The haplotype reconstruction revealed a shared 264.4-kb region among carriers from all six countries. The estimated mutation age was similar to 100 generations in Iberia and that it was introduced to South America early during the European colonization period. Conclusions: Our results suggest that this mutation originated in Iberia and later introduced to Colombia and South America at the time of Spanish colonization during the early 1500s. We also found that the Colombian mutation carriers had higher European ancestry, at the BRCA1 gene harboring chromosome 17, than controls, which further supported the European origin of the mutation. Understanding founder mutations in diverse populations has implications in implementing cost-effective, ancestry-informed screening

Soft skills y clima laboral en los colaboradores de la Unidad de Gestión Educativa Local San Martín – Tarapoto 2020

La presente investigación tuvo como objetivo, determinar la relación entre las soft skills y el clima laboral en los colaboradores de la Unidad de Gestión Educativa Local San Martín, Tarapoto 2020 el cual es correspondiente a la carrera de psicología en el ámbito organizacional. La investigación fue de diseño básico de tipo no experimental transversal correlacional; la muestra estuvo constituida por 60 colaboradores de las distintas áreas de trabajo de la UGEL San Martín a quienes se les aplicó dos cuestionarios, Habilidades Blandas de Luis A. Franco Saldaña y la Escala de Clima Laboral de Sonia Palma CL - SPC. Se utilizó el Coeficiente de Correlación de Pearson, en donde se encontró que existe una correlación significativa positiva de intensidad considerable entre las soft skills y el clima laboral en los colaboradores de la UGEL San Martín, Tarapoto 2020. Los resultados que se obtuvieron en la presente investigación son datos relevantes e importantes que servirán como base para investigaciones realizadas en el futuro enfocadas a éste ámbito, debido a que, tiene como elemento principal el estudio del individuo y su desenvolvimiento dentro de las organizaciones

Propuesta e implementacion de mejora en el proceso de produccion de elementos verticales estructurales internos en una edificacion de una empresa constructora

El presente proyecto se basa en el estudio de la mejora del proceso de elaboración de elementos verticales estructurales internos de una empresa constructora que ejecuta proyectos de vivienda. Dichos elementos presentaban un alto porcentaje de no conformidades, lo que provocaba reprocesos y sobrecostos. El objetivo de este proyecto es la reducción de estas no conformidades. Para poder resolver este problema se realizó una propuesta de mejora e implementación que logró el objetivo. En el capítulo uno se desarrolla el marco teórico, el cual contiene términos y conceptos que ayudarán a la mejor comprensión de los siguientes capítulos. Para el desarrollo del segundo capítulo, se describió la situación inicial, análisis, costos de reparación, problema e hipótesis. Para el desarrollo del tercer capítulo se presenta las propuestas de mejora. Finalmente, en el cuarto capítulo se realizó la validación de la propuesta a través de la implementación y se muestra los resultados obtenidos.The present project is based on the study of the improvement of the production process of vertical structural elements of a construction company that executes housing projects. These elements presented a high percentage of non-conformities, which caused reprocessing and cost overruns. The objective of this project is the reduction of these non-conformities. In order to solve this problem, an improvement and implementation proposal was made that achieved the objective. In chapter one the theoretical framework is developed, which contains terms and concepts that help to better understand the following chapters. For the development of the second chapter, description of the initial situation, analysis, repair costs, problem and hypothesis. For the development of the third chapter, the improvement proposals are presented. Finally, in the fourth chapter the validation of the proposal was carried out through the implementation and the results obtained were shown.Tesi

Análisis de ADN mitocondrial en momias del norte de Chile avala hipótesis de origen amazónico de poblaciones andinas mtDNA analysis of mummies from northern Chile endorse the hypothesis of an Amazonian origin of Andean populations

La hipótesis del origen amazónico de las poblaciones andinas basada en el análisis de marcadores genéticos nucleares es contrastada haciendo uso de ADN mitocondrial antiguo aislado de restos esqueletales de poblaciones prehistóricas del Valle de Azapa, Arica, Chile. Se analizaron 42 muestras de las cuales 32 rindieron amplificados para los cuatro marcadores amerindios permitiendo su tipificación. La distribución de haplogrupos (A: 31,2 %, B: 21,9 %, C: 31,2 %, D: 3,1 % y otros 12,5 %) relaciona genéticamente a las poblaciones estudiadas con grupos amazónicos y andinos actuales. El número de muestras analizadas no permite aún una subdivisión por fases cronológicas con el objeto de poner a prueba las hipótesis planteadas por arqueólogos y bioantropológos para explicar la microevolución biocultural de las poblaciones estudiadasThe Amazonian origin of Andean populations, hypothesized on the basis of nuclear genetic markers, is tested using ancient mtDNA extracted from skeletal remains from prehistoric populations of the Azapa valley, northern Chile. Forty two samples were analyzed of which 32 could be typed for Amerindian haplogroups whose distribution (A: 31.2 %, B: 21.9 %, C: 31.2 %, D: 3.1 % and others 12.5 %) relates genetically the prehistoric groups to Amazonian and living Andean populations. The number of samples is still to small to allow a subdivision by chronological phases in order to test hypothesis about the biocultural microevolution of the populations studie